Aquaporin-4 Expression during Toxic and Autoimmune Demyelination
| Autor: | Paul van der Valk, Christoph Schmitz, Sarah Joost, Sandra Amor, Sven Olaf Rohr, Markus Kipp, Theresa Greiner |
|---|---|
| Přispěvatelé: | Pathology, AII - Inflammatory diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Pathology
medicine.medical_specialty experimental autoimmune encephalomyelitis neuromyelitis optica Blood–brain barrier blood–brain barrier multiple sclerosis Article Autoimmune Diseases Myelin Mice Immune system medicine Animals Humans digital histology aquaporin 4 lcsh:QH301-705.5 Myelin Sheath Inflammation Neuromyelitis optica business.industry Multiple sclerosis Experimental autoimmune encephalomyelitis Brain General Medicine medicine.disease cuprizone Disease Models Animal Aquaporin 4 medicine.anatomical_structure Gene Expression Regulation lcsh:Biology (General) Brain Injuries demyelination sense organs business Astrocyte Demyelinating Diseases |
| Zdroj: | Cells, 9(10). MDPI Multidisciplinary Digital Publishing Institute Cells, Vol 9, Iss 2187, p 2187 (2020) Cells Volume 9 Issue 10 Rohr, S O, Greiner, T, Joost, S, Amor, S, Valk, P V D, Schmitz, C & Kipp, M 2020, ' Aquaporin-4 Expression during Toxic and Autoimmune Demyelination ', Cells, vol. 9, no. 10 . https://doi.org/10.3390/cells9102187 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9102187 |
| Popis: | The water channel protein aquaporin-4 (AQP4) is required for a normal rate of water exchange across the blood&ndash brain interface. Following the discovery that AQP4 is a possible autoantigen in neuromyelitis optica, the function of AQP4 in health and disease has become a research focus. While several studies have addressed the expression and function of AQP4 during inflammatory demyelination, relatively little is known about its expression during non-autoimmune-mediated myelin damage. In this study, we used the toxin-induced demyelination model cuprizone as well as a combination of metabolic and autoimmune myelin injury (i.e., Cup/EAE) to investigate AQP4 pathology. We show that during toxin-induced demyelination, diffuse AQP4 expression increases, while polarized AQP4 expression at the astrocyte endfeet decreases. The diffuse increased expression of AQP4 was verified in chronic-active multiple sclerosis lesions. Around inflammatory brain lesions, AQP4 expression dramatically decreased, especially at sites where peripheral immune cells penetrate the brain parenchyma. Humoral immune responses appear not to be involved in this process since no anti-AQP4 antibodies were detected in the serum of the experimental mice. We provide strong evidence that the diffuse increase in anti-AQP4 staining intensity is due to a metabolic injury to the brain, whereas the focal, perivascular loss of anti-AQP4 immunoreactivity is mediated by peripheral immune cells. |
| Databáze: | OpenAIRE |
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